The overall objective of this project is to investigate the influence of cadmium on mammalian biochemical systems in an effort to understand certain parameters associated with a cadmium toxicity. This will be accomplished by investigating: a. The mechanism of cadmium-metallothionein synthesis. This phase will involve experiments on the cell-free synthesis of cadmium-metallothionein and the mRNA responsible for regulation of the rate of binding protein synthesis in liver, kidney and other tissues including intestinal mucosa. b. The mechanism of cadmium absorption. This phase will establish the role of mucosal cell cadimum binding protein, the nature of the regulation of its synthesis, and its role in the intramucosal translocation process and cadmium absorption. c. The influence of dietary cadmium on iron metabolism. The uptake and distribution of radioiron will be determined to establish the site of action of cadmium that results in the depleted iron stores and anemia associated with this toxicity. d. The influence of dietary calcium level on cadmium metabolism. Graded levels of dietary calcium will be fed to establish the level of dietary calcium restriction necessary to develop a toxicity. The length of time from starting low calcium feeding until a toxicity develops will be determined.